Chemokine CXCL1 may serve as a potential molecular target for hepatocellular carcinoma

Abstract

The purpose of this study was to screen for changes in chemokine and chemokine‐related genes that are expressed in hepatocellular carcinoma (HCC) as potential markers of HCC progression. Total RNA was extracted from tumor and peritumor tissues from mice with HCC and analyzed using a PCR microarray comprising 98 genes. Changes in gene expression of threefold or more were screened and subsequently confirmed by immunohistochemical analyses and western blotting. Furthermore, whether chemokine knockdown by RNA interference (RNAi) could significantly suppress tumor growth in vivo was also evaluated. Finally, total serum samples were collected from HCC patients with HBV/cirrhosis (n = 16) or liver cirrhosis (n = 16) and from healthy controls (n = 16). The serum mRNA and protein expression levels of CXCL1 in primary liver cancer patients were detected by qRT‐PCR and western blot analysis, respectively. Several genes were up‐regulated in tumor tissues during the progression period, including CXCL1, CXCL2, CXCL3, and IL‐1β, while CXCR1 expression was down‐regulated. CBRH‐7919 cells carrying CXCL1 siRNA resulted in decreased tumor growth in nude mice. The differences in serum CXCL1 mRNA and protein levels among the HCC, hepatic sclerosis (HS), and control groups were significant (P < 0.001). The mRNA and protein levels of CXCL1 in the HCC group were up‐regulated compared with the HS group or the control group (P < 0.001). Several chemokine genes were identified that might play important roles in the tumor microenvironment of HCC. These results provide new insights into human HCC and may ultimately facilitate early HCC diagnosis and lead to the discovery of innovative therapeutic approaches for HCC.

CXCR2‐modified CAR‐T cells have enhanced trafficking ability that improves treatment of hepatocellular carcinoma

“…In our study, we found that in hepatocellular carcinoma tumors, several CXCR2 ligands, CXCL1, CXCL2, CXCL5, and CXCL8 showed relatively high expression level. Coincidentally, previous studies reported that abnormally expression of these chemokines was involved in tumor proliferation, invasion, and prognosis of HCC . These findings indicate that CXCR2 ligands may play crucial role in HCC development or tumorigenic maintenance.…”

Different Effects of Human Umbilical Cord Mesenchymal Stem Cells on Glioblastoma Stem Cells by Direct Cell Interaction or Via Released Soluble Factors

“…GROs were initially isolated from the CM of a melanoma cell line (Richmond and Thomas, 1988 ) and their role in promoting tumorigenesis was identified in several tumors. Downregulation of CXCR1 and CXCR2, by interfering siRNA, inhibits melanoma tumor growth and cell invasion (Singh et al, 2010 ); similarly RNAi of GROα suppresses tumor growth in hepatocellular carcinoma (Han et al, 2016 ). In GBM cell lines, GROα promotes tumor growth, in vitro cell motility and invasiveness and enhances tumor cell spread in vivo (Zhou et al, 2005 ).…”

NLRC and NLRX gene family mRNA expression and prognostic value in hepatocellular carcinoma

“…Its sensitivity for HCC screening ranges from 41 to 65% at a cutoff of 20 ng/mL . In recent years, various biomarkers have emerged for diagnosing HCC and predicting patient outcome, including glypican 3 and insulin‐like growth factor (IGF)II mRNA , Keap1 and pNrf2 , 3‐microRNA and AFP , CXCL1 , minichromosome maintenance complex ‐7 , and IGF1 receptor , among others.…”